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Subjects

Abstract

Hemospermia is known to be associated with transrectal ultrasound-guided prostate biopsy (TRUS-PB). The true incidence of hemospermia, its duration and implications are not well established. We performed a prospective observational study involving patients undergoing TRUS-PB for suspected prostate cancer at our institution. Sixty-three eligible men were included in the study. Most men (84%) undergoing TRUS-PB, who were able to ejaculate, experienced hemospermia, which was associated with some degree of anxiety. The mean duration of hemospermia was 3.5 (±1.7) weeks. The number of ejaculations before the complete resolution of hemospermia was 8 (±6.7). None of the clinical and pathological factors was a significant predictor of the duration of hemospermia. Patients should be adequately counseled before TRUS-PB to avoid undue anxiety and alterations in sexual activity.

Introduction

In the prostate-specific antigen (PSA) era, increasing numbers of patients are being evaluated for suspected prostate cancer.1 Transrectal ultrasound (TRUS)-guided prostate needle biopsy (PB) is a simple and reliable technique to obtain prostatic tissue for histological evaluation.2, 3, 4 Most men with elevated PSA or abnormal digital rectal examination (DRE) undergo TRUS-PB. In the face of low morbidity, the TRUS-PB is performed as an outpatient procedure.2, 5, 6, 7

Although the incidence of major complications associated with TRUS-BP is low, minor complications such as urinary tract infection, dysuria, hematuria and hemospermia are frequent.2, 6 Although many studies have reported the incidence of complications, they were not specifically designed to evaluate the true complication rate and its implications.8, 9, 10, 11, 12 It is essential to have a clear understanding of the true morbidity of this procedure, and this would enable appropriate patient counseling.

Hemospermia is a well-recognized complication of TRUS-guided prostate biopsy. Although it is classified under minor complications, its persistence causes immense distress to the patient and the partner. The true incidence, duration and its repercussions after TRUS-PB are not well understood. Most studies on complications of TRUS-PB were retrospective in nature and very few addressed hemospermia in detail. In this study we prospectively evaluated patients undergoing PB for hemospermia and its implications.

Methods

With institutional review board's approval, we performed at our institution, a prospective observational study involving patients undergoing TRUS-guided prostate biopsy for suspected prostate cancer, over a 6-month period. Men who were not able to ejaculate were excluded from the study. Men were instructed not to take aspirin or non-steroidal anti-inflammatory agents for at least 5 days before the procedure.

After informed consent was obtained, demographic and clinical information were collected through a pre-biopsy questionnaire. All patients were started on 3-day course of a fluroquinolone antibiotic before the procedure. No pre-biopsy bowel preparation or cleansing enema was used.

The patient was positioned in left lateral decubitus position. A digital rectal examination was performed before the start of the procedure. TRUS was performed with a bipolar 7.5 MHz probe (Siemens, Erlangen, Germany). The prostate volume was calculated with the prolate ellipsoid formula (volume=0.52 × length × breadth × height).13, 14 Prostate gland was scanned on longitudinal and sagittal planes for any sonographic abnormalities such as hypoechoic areas. A 10 ml volume of 1% lignocaine was injected into periprostatic space under sonographic guidance. Systematic biopsies were performed in the sagittal plane with an 18-gauge biopsy needle driven by a spring-loaded biopsy gun (Bard, Georgia) under ultrasound guidance. All men had standard peripheral sextant pattern biopsy and two additional cores from the transition zone on each side, making a total of 10 cores.

Any immediate complication after the procedure was recorded. All patients enrolled in the study were encouraged to ejaculate at least once a week either by sexual activity or self-stimulation. The color of the semen was observed and noted by the patient until the color is normal on three consecutive occasions. The color of the semen was noted as bloody, altered or normal color. Patients were handed a validated questionnaire to obtain data on the duration and impact of hemospermia on anxiety levels and sexual activity. The anxiety scores were recorded using a visual analog scale (0 – no anxiety; 10 – extreme anxiety). Patients were subsequently contacted over telephone to ascertain the accuracy and completeness of the data collection. Those patients who did not return the questionnaire were contacted at the end of 8 weeks from biopsy to complete the follow-up. Relevant clinical and pathological data such as PSA, number of biopsy cores, repeat biopsies and other co-morbidities were collected and entered in a database. Statistical analysis was performed with t-test and χ2 tests to assess the predictive ability of the variables.

Results

Over a period of 6 months, 63 eligible consecutive patients who underwent TRUS-PB were included in the study. The mean age was 61.5 (±8) years. Twelve patients (19%) had positive biopsy for prostate cancer. All men completed the pre-biopsy questionnaire. Forty-one men (65%) completed the study providing adequate data. Three patients did not ejaculate, and hence were not included in the analysis. The mean PSA was 6.9 (±9) ng/ml. All patients had 10 cores biopsy, except one who had two additional cores from sonographically suspicious area. The mean estimated volume of the prostate was 52 (±24) ml. Five men (13%) had previously undergone prostate biopsy. No patient had any history of bleeding disorder. Four (6%) had past history of prostatitis. None had any history of hemospermia within 6 months before the date of procedure.

Thirty-eight men ejaculated in the first week. Thirty-two of these men (84%) reported hemospermia during the first week. Twenty-five of these (78%) reported that the semen was red in color and seven (22%) reported altered color. During the second week, 25 men (66%) reported hemospermia. Six and nineteen of these men noticed red (24%) and altered color (76%) ejaculate, respectively. Seven men (22%) who had blood in the ejaculate during the first week, reported no hemospermia in the second week.

At the end of 4 weeks, 12 men (32%) had continued abnormal-colored ejaculate. Two men (16%) noticed red colored ejaculate and 10 men (84%) noticed altered color. After 4 weeks, none had red-colored ejaculate and all men who reported hemospermia had altered color of the semen. At 8 weeks, one man (2.6%) had persistently altered blood in the ejaculate, but this cleared in 10 weeks. Table 1 summarizes the incidence of hemospermia during the post-biopsy period.

The mean duration of hemospermia was 3.5 (±1.7) weeks. The number of ejaculations before the complete resolution of hemospermia was 8 (±6.7). The mean anxiety score was 1.8 (±2.7). Sixteen men (50%) reported less sexual activity due to hemospermia following the biopsy. No clinical and pathological factors, such as age, repeat biopsy, PSA, number of cores, presence of cancer and history of prostatitis, had any correlation with the incidence or duration of hemospermia. However, the anxiety scores and the number of ejaculations had positive correlation with the duration of hemospermia (P=0.04; P=0.047).

Discussion

Transrectal ultrasound-guided biopsy of the prostate is a well-accepted, safe and rapid technique for prostate cancer diagnosis.2 It is generally well tolerated, with no sedation, by most men. The reported major complication rate is less than 1%.2, 15 In contrast, minor complications are frequent, with 60–79%.5, 16 Most of these complications do not require any intervention and are self-limiting. However, it is essential to have a clear understanding of the true morbidity of this procedure to counsel the patient accordingly.

Hemospermia is a distressing symptom in sexually active men.17 It is defined as the presence of fresh or altered blood in the ejaculate. In most cases, it is caused by nonspecific inflammation of the prostate and seminal vesicles.18 Occasionally, it may be the sole manifestation of underlying genito-urinary disease.19 Other causes of hemospermia include glandular ductal obstruction and cyst formation, genito-urinary malignancies and vascular and hematalogical abnormalities. However, currently the most common etiology of hemospermia is iatrogenic.17 Interventions such as prostate biopsy, radiation therapy to prostate, brachytherapy, high-intensity focus ultrasound therapy, intraprostatic injection of medications and urethral foreign bodies may be associated with hemospermia.10, 20 This symptom provokes profound anxiety in men and makes them seek medical advice earlier.21 The reported incidence of hemospermia after TRUS-PB varies between 5.1 and 89%.6, 22

The prospective European prostate cancer detection (EPCD) study evaluated the safety, morbidity and complication rates of first and repeat TRUS-PB. In this large series, 1051 men underwent first biopsy and subsequently 820 men had repeat biopsy in 6 weeks interval. One hundred and threemen (9.8%) after the first biopsy and 84 men (10.2%) after the repeat biopsy reported hemospermia.2 There was no significant difference in the incidence of hemospermia between the two groups. Naugthon et al. prospectively studied the impact of number of cores on the morbidity caused by TRUS-PB. They reported that 89% (n=71) of 12 core group and 71% (n=57) of 6 core group had hemospermia.6 De la Taille et al.23 prospectively evaluated the cancer detecting ability of the 21 sample needle biopsy with 303 men and reported 60% incidence of hemospermia in post-biopsy period. There was no significant difference in the incidence of hemospermia between symptomatic patients having biopsy subsequent to hospital referral and patients attending screening clinics. Mankinen et al.24 reported this after studying 200 men, with the incidence of hemospermia between 52 and 45% among the study groups. In the current series, 84% of men had hemospermia during the first week after the biopsy. Table 2 shows the various studies and the incidence of hemospermia.

Review of literature showed that the reported incidence of hemospermia varies from 5.1 to 89%.6, 22, 25 The reason for the wide range in the incidence of hemospermia may be multifactorial. Many of the studies did not eliminate the patients who were not able to ejaculate. This could have contributed to a false low-incidence of this complication. In addition, the reported incidence of hemospermia in many of the retrospective studies was low.9, 22, 26, 27 On the other hand, most prospective studies reported higher incidence of hemospermia when compared to retrospective studies.6, 23, 24 This may well be due to recall bias and insufficient data collection in retrospective studies. In most series, the proportion of men ejaculated before the follow-up interview was not available, and this could reflect on the true incidence of this complication. Moreover, few investigators considered hemospermia as a delayed complication and recorded only men with persistent hemospermia as an adverse event.2, 28 In our study, the incidence of hemospermia was 84% in the first week after biopsy. Elimination of patients who were not able to ejaculate and emphasis on hemospermia during counseling could have attributed to the higher reporting of this complication. The anxiety scores due to hemospermia were low in our study. Pre-biopsy counseling with reassurance could have affected the true anxiety levels. Most men in our study expressed that they would have been more concerned about hemospermia had they not been counseled.

Hemospermia was considered as a moderate or major problem in approximately 17% of men in Naughton et al.'s prospective study. In our study, 50% of men said that they had less than normal sexual activity due to hemospermia during the first 8 weeks of post-biopsy period. The mean duration of spontaneous resolution of hemospermia was 3.5 weeks. De la Taille et al.23 reported 12.8 days as the mean duration for resolution of hemospermia. Rodriguez et al.7 observed persistent hemospermia over a month in 10% of men after TRUS-PB. Naughton et al. showed significantly higher incidence of hemospermia with 12 core (89%) biopsy when compared with six core (71%) technique. In contrast, De la Taille et al.23 studied 303 patients with 21 core biopsy and reported 60% hemospermia. Reitbergen et al.25 demonstrated that hemospermia and hematuria were less frequently seen in men with prostate cancer in the biopsy specimen. This phenomenon remains uncertain and it is not reproduced in any other study. There is no proven increase in hemorrhagic complications with aspirin or other non-steroidal anti-inflammatory drug use.7, 29 In our study none of the clinical and pathological character was able to predict the incidence or duration of hemospermia. However, the number of ejaculations correlated with the duration of hemospermia, which may be a simple analytical correlation.

In summary, hemospermia is a frequent complication of TRUS-PB. Hemospermia following TRUS-PB is mostly self-limiting. Mean duration of hemospermia is 3.5 weeks and in small percentage it may persist over 4 weeks. This symptom may result in significant patient and partner anxiety. Therefore patients should be counseled about this complication adequately. We recognize that there are few limitations to this study. Although the study is prospective in nature, it was not stratified to evaluate the impact of co-morbidities. The pre-biopsy counseling on complications with more emphasis on hemospermia would have reduced the threshold for reporting this complication. More detailed randomized large sample prospective trials are necessary to validate the incidence of hemospermia.

Conclusion

Transrectal ultrasound-guided prostate needle biopsy is a safe and well-accepted office procedure for diagnosis of prostate cancer. Most complications of this procedure are mild and self-limiting. Most men (84%) undergoing TRUS-PB, who are able to ejaculate, will experience hemospermia, which is associated with some degree of anxiety and impact on sexual activity. Patients should be adequately counseled before TRUS-PB to avoid undue anxiety and alterations in sexual activity.